Carboxylated methyl cellulose with quaternary ammonium compound as topical remedy



Patented Feb. 12, 1952 oAnBoXYL TEoMErnyL CELLULOSE WITH QUATERNARY AMMoNrU COMPOUND AS TOPICAL REMEDY Herman A. Shelanski, Philadelphia, -Pa., assignor to Onyx Oil,& Chemical Company, Jersey City, N. 3., a corporation of Delaware No Drawing. Application April 8, 19 19, Serial No. 86,405

6 Claims. i

This invention relates :to a medicinal preparation comprising new compositionsof matter more particularly adapted for use in the treatment of bacterial fungus, protozoan and ,metazoan infections in man and animals.

Compositions according to this invention include essentially a quaternary ammonium c. 1 1- pound, the alkyl chain of which has 8-18 carbon atoms, and a sodium salt of carboxylated methyl cellulose.

Quaternary ammonium salts are known to have a germicidal and fungicidal effect and to have variously been used heretofore in the treatment of bacteria and fungi infections in man and animals. Such compounds, while effective, have in such use heretofore been open to the serious objection that it has been impractical to effectively apply them to affected tissue, especially where the tissue is in the form of folds and cavities, and for the reason that their effect is of short duration requiring for efficacy repeated applications at short intervals.

Compositions according to this invention are believed to be reaction products of a quaternary ammonium salt and a sodium salt of 'carboxylated methyl cellulose, in that there appears to be a chemical linkage between the two. However, in any .event, the compositions have proved to be of great efiicacy in the treatment of bacteria and fungi infections in that, in the form of a ference with the breathing of the tissue or the function of the pores and, in the presenceof body" fluids, the formation of a gelatinous .n'lass with gradual controlled release therefrom of the active germicidal and bactericidal principle, it is be.- lieved, through ionic exchange with e1ectrolytes present in the body fluids or mucus. The compositions may also be administered by mouth with similar effect upon internal The compositions according to this inyention enable the effective treatment of bactenia andfungi infections without interference with normal functioning of tissue and with maintenance of a high germicidal and bactericidal level over long periods.

The compositions variously will be found especially effective, for example, for the treatment of protozoan infections, such as, for example, trichomonas, amoebas, sporazoas, and the like; .and for the treatment, for example, of helminth infections, such as, for example, nematodes,

cestodes, trematodes, and the like.

The efficacy of compositions according to this invention, involving the combination of a quaternary ammonium salt with a sodium salt of carboxylated methyl cellulose, is most surprising when it is considered that usually the anti-bacterial effect of compounds comprising surfaceactive cations and an anion of low molecular weight is greatly diminished or even eliminated when such compounds are mixed with high-molecular weight anionic compounds. This is borne out by the fact that the instruction sheets for the use of surface-active cationic germicides ordinarily contain a warning against mixing with substances containing high molecular weight anions. Thus, it has been noticed that upon mixing of the two kinds of materials in aqueous solutions, a precipitate "is usually formed which is, undoubtedly, an insoluble salt representing a combination of the high molecular weight cations with the high molecular weight anion. That the partial or complete loss of germicidal power fol.- lows as a consequence of this metathe'tic reaction seems clear.

In preparing compositions according to this invention quaternary ammonium salts having 8-18 carbon atoms in the alkyl chain will be used and such compounds having a phenol coefiicient greater than 50, when tested at 20 C. against Staphylococcus aureus and- Eberthellc typhosa by the procedure described in circular #198 of the United States Department of Agriculture, will be preferred. Desirably the quaternary ammonium salt will be one having a phenol coefficient above 100, when tested as above.

Preferentially the quaternary ammonium salt will be 3,4-dichlorobenzyl dimethyl dodecyl ammonium chloride, since such will be especially eflicacious in that, quite unexpectedly, it has been found it will be effective to an optimum degree in an acid medium such as is found-in the vaginal tract.

In preparing compositions according to this invention the quaternary ammonium salt will be used in amount within about the range -.01-'3.0 parts by weight to about 99.99-9'120 parts by weight or preferably within the narrower ratio of 1.0-3 to 99.0-97.0 of the water-soluble metal salt of carboxylated cellulose.

Compositions variously may contain more than one quaternary ammonium salt, but in such case the additional salt, or salts, will not exceed about 20-30% of the total weight of the salt content of r the composition. By way of example a preferential composition for use in the presence of an acid medium, as in the vaginal tract, will include a mixture of 3,4-dichlorobenzyl dimethyl dodecyl ammonium chloride and dimethyl ethyl 9-octadecenyl ammonium bromide, the mixture comprising about 20-30% of the latter salt.

Compositions according to this invention may be conveniently prepared by dissolving the quaternary ammonium salt, or salts, as defined, and a sodium salt of carboxylated methyl cellulose in a common solvent, as water, ethyl alcohol, or the like, and air drying, or, again, :by mixing a sodium salt of carboxylated methyl cellulose into an aqueous or alcoholic solution of the quaternary ammonium salt and evaporating to dryness.

The compositions variously will be in the form of powder, a jelly or a gum, depending upon the particular components used in their preparation. For many purposes the powder form will be desirable, since it lends itself to administration by insufliation, as is desirable in the treatment of, for example, trichomonas vaginalis vaginitis.

As examples of specific compositions according to this invention and of procedure for their preparation, the following will be illustrative:

Example 1 To 99 parts by weight of powdered sodium carboxyl methyl cellulose (medium viscosity) prepared from cotton linters are added 18 parts of a solution containing 1 part of 3,4-dichlorobenzyl dimethyl dodecyl ammonium chloride, 3 parts of water and 16 parts isopropyl alcohol. The mixture is treated in a dough mixer or kneader for one hour and thereafter air dried until 'most of the liquid evaporates, the water and alcohol being merely vehicles facilitating the mixing. The resulting material is a free-flowing powder suitable for the treatment of trichomonas vaginalis vaginitis by insufliation.

Example 2 Three parts by weight of an 80-20 mixture of 3,4-dichlorobenzyl dimethyl dodecyl ammonium chloride and dimethyl ethyl Q-octadecenyl ammonium bromide and 97 parts of the sodium carboxyl methyl cellulose are added to one part of isopropyl alcohol and 16 parts water. The mixture is treated as in Example 1, to obtain a freefiowing powder similarly suitable for the treatment of the vaginitis by insufilation.

Example 3 The composition is prepared by the procedure of Example 2 substituting dimethyl benzyl dodecyl ammonium chloride or dimethyl benzyl ptertiary octylphenoxyethoxyethyl ammonium chloride for the dimethyl ethyl Q-octadecenyl ammonium bromide. It is again free-flowing and readily administered by insufilation in the treatment of the vaginitis.

This application is a continuation-in-part of an application filed by me June 27, 1947, Serial No. 757,685, now abandoned.

What I claim and desire to protect by Letters Patent is:

1. A medicinal preparation for the treatment of protozoan infections, and the like, comprising an active protozoacide comprising a mixture of 3,4-dichlorobenzyl dimethyl dodecyl ammonium chloride in the amount of -80% and dimethyl ethyl 9-octadeceny1 ammonium bromide in the amount of 30-20% in admixture with the sodium salt of carboxylated methyl cellulose in the proportion of about 99.0-97.0 parts by weight to 1.0-3.0 parts by weight of the active protozoacide.

2. A medicinal preparation for the treatment of protozoan infections, and the like, comprising a mixture of 3,4-dichlorobenzyl dimethyl dodecyl ammonium chloride and dimethyl ethyl 9-octadecenyl-ammonium bromide in the proportion of about %-20% in admixture with the sodium salt of carboxylated methyl cellulose.

3. A medicinal preparation for the treatment of protozoan infections, and the like, comprising a mixture of 3,4-dichlorobenzyl dimethyl dodecyl ammonium chloride and dimethyl ethyl 9-octadecenyl ammonium bromide in admixture with the sodium salt of carboxylated methyl cellulose.

4. A medicinal preparation for the treatment of protozoan infections, and the like, comprising a mixture of 3,4-dichlorobenzyl dimethyl dodecyl ammonium chloride in the amount of 70-80% and dimethyl ethyl 9-octadecenyl ammonium bromide in the amount of 30-20% in admixture with the sodium salt of carboxylated methyl cellulose.

5. A medicinal preparation according to claim 3, characterized by the fact that the preparation is in the form of a dry powder.

6. A medicinal preparation according to claim 3, characterized by the fact that the preparation includes a solvent for the sodium salt of carboxylated methyl cellulose and is in the form of a, jelly.

HERMAN A. SHELANSKI.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 2,314,277 Hurd Mar. 16, 1943 2,321,270 Bacon June 8, 1943 2,484,637 Mattocks Oct. 11, 1949 FOREIGN PATENTS Number Country Date 187,941 Switzerland Nov. 30, 1936 806,662 France Dec. 22, 1936 OTHER REFERENCES Gutman, Modern Drug Ency., York Pub. Co., Inc. N. Y., 3rd ed., June 1946, pages 167-168.

Johnson, Proc. Exptl. Biol. 8.: Med., Nov. 1943, pp. 245-248.

Kanski, Am. J. Surgery, Oct. 1946, pp. 580-582.

Hollabaugh, Industrial & Eng. Chem, Oct. 1945, pp. 943-945.

Mattooks et al., J. A. P. A. Scien. Ed., Sept. 1946.

New and Nonoflicial Remedies, pp. 113-114, J. P. Lippincott, 1950, Phila. 

1. A MEDICINAL PREPARATION FOR THE TREATMENT OF PROTOZOAN INFECTIONS, AND THE LIKE, COMPRISING AN ACTIVE PROTOZOACIDE COMPRISING A MIXTURE OF 3,4-DICHLOROBENZYL DIMETHYL DODECYL AMMONIUM CHLORIDE IN THE AMOUNT OF 70-80% AND DIMETHYL ETHYL 9-OCTADECENYL AMMONIUM BROMIDE IN THE AMOUNT OF 30-20% IN ADMIXTURE WITH THE SODIUM SALT OF CARBOXYLATED METHYL CELLULOSE IN THE PROPORTION OF ABOUT 99.0-97.0 PARTS BY WEIGHT TO 1.0-3.0 PARTS BY WEIGHT OF THE ACTIVE PROTOZOACIDE. 